EPSTEIN-BARR VIRUS IN HODGKIN'S DISEASE

这一小型赠款项目将扩大正在进行的、由NCI资助的流行病学 旧金山湾区霍奇金病(HD)病例对照研究 通过收集和纳入关于EB病毒(EBV)的数据 病例受试者肿瘤细胞。EBV最近被牵连为一种 在大约一半的HD肿瘤中存在致病辅助因素。因此，高清可能是 可细分为EBV阳性和EBV阴性，将EBV数据添加到 正在进行的研究将加强对生殖的初步调查 通过提供更精确的疾病终端(即HD)来确定风险因素 由EBV状态定义的子组。这个小型赠款项目的目标是： 1)收集正在进行的病例研究对象的存档肿瘤标本 研究、应用标准分子病毒学技术鉴定EBV HD肿瘤细胞中的潜伏基因产物，并将每个病例对象分类为 EBV阳性或EBV阴性；2)确定生殖风险，例如， 对于EBV阳性和EBV阳性的妇女来说，产次的保护作用不同 阴性HD；3)描述EBV阳性和EBV- 年龄、种族和组织亚型的阴性HD，并探讨 与各种附加因素相关的两个病毒定义的亚组 正在被衡量，包括增加HD的社会阶层特征 风险。正在进行的研究最终将涉及315名患有HD的女性和315名患有HD的女性 人口控制在面对面的采访中，涉及人口统计， 生殖、激素使用、社会阶层、家庭、医疗和其他 生活方式主题。HD的诊断和组织学分类正在进行中 对准确性进行了审查。到目前为止，96%的受邀案例对象已经 采访过了。 对于小额赠款项目，我们将要求受访对象的肿瘤 来自病理学家的组织样本；在一项初步研究中，我们已经获得了 约85%的受试者的标本。接触肿瘤标本是时候了- 有限，因为它是基于受试者签署的同意释放 正在进行的研究的病理材料，很快就会完成。 样本将被邮寄给我们的合作调查员，他将测试部分 EBV潜伏基因产物的聚合酶链式反应 杂交和免疫过氧化物酶技术检测LMP-1， 阳性对照和阴性对照。这种杂交方法很灵敏， 一致，快速，不产生细胞或其他疱疹病毒交叉- 杂交。数据分析将表征EBV阳性和EBV- 负HD by当前正在调查的变量，使用描述性 统计数据。多元统计方法将估计和比较 EBV阳性和EBV阴性HD的优势比与 生殖和其他危险因素，调整后为疑似 混血儿。作为最早结合分子病毒学的研究之一 以及基于人群的HD系列中广泛的个人风险因素数据 病例，这个小型赠款项目将提供初步的流行病学 多种方法对EBV阳性和EBV阴性HD的评价 假定和确立的特征会增加这种风险 淋巴瘤。

This Small Grant project will expand an ongoing, NCI-funded, epidemiologic case-control study of Hodgkin's disease (HD) in San Francisco-Bay Area women by collecting and incorporating data on Epstein-Barr virus (EBV) in tumor cells of case subjects. EBV recently has been implicated as a pathogenetic cofactor in about one-half of HD tumors. As HD thus may be subclassifiable as EBV-positive and EBV-negative, addition of EBV data to the ongoing study will enhance its primary investigation of reproductive risk factors by providing more precise disease endpoints, i.e., HD subgroups defined by EBV status. The aims of this Small Grant project are: 1) to collect archived tumor specimens from case subjects in the ongoing study, apply standard molecular virologic techniques to identify EBV latent gene products in HD tumor cells, and classify each case subject as EBV-positive or EBV-negative; 2) to determine if reproductive risks, e.g., a protective effect of parity, differ for women with EBV-positive and EBV- negative HD; 3) to describe the distribution of EBV-positive and EBV- negative HD by age, race, and histologic subtype, and explore risks for the two virus-defined subgroups associated with various additional factors being measured, including social class characteristics that increase HD risk. The ongoing study ultimately will involve 315 women with HD and 315 population controls in in-person interviews covering demographic, reproductive, hormone-use, social class, familial, medical, and other lifestyle topics. Diagnosis and histologic classification of HD are being reviewed for accuracy. To date, 96% of invited case subjects have been interviewed. For the Small Grant project, we will request interviewed subjects' tumor tissue specimens from pathologists; in a pilot study, we have acquired specimens for about 85% of subjects. Access to tumor specimens is time- limited, as it is based on signed consent from subjects to release pathologic materials for the ongoing study, soon to be completed. Specimens will be mailed to our coinvestigator, who will test sections for EBV latent gene products using polymerase chain reaction, EBER in situ hybridization, and immunoperoxidase techniques to detect LMP-1, with positive and negative controls. This hybridization method is sensitive, consistent, rapid, and produces no cellular or other herpesvirus cross- hybridization. Data analysis will characterize EBV-positive and EBV- negative HD by variables presently under investigation, using descriptive statistics. Multivariate statistical methods will estimate and compare odds ratios for EBV-positive and EBV-negative HD associated with reproductive and other risk factors, after adjustment for suspected confounders. As one of the first studies to combine molecular virologic and extensive personal risk factor data in a population-based series of HD cases, this Small Grant project will provide initial epidemiologic evaluation of EBV-positive and EBV-negative HD by a variety of characteristics postulated and established to increase risk of this lymphoma.